The invention relates to a method and a device which reduces the phase space volume of ions in an ion beam in such a way that their injection into a downstream time-of-flight mass spectrometer optimizes the performance of that spectrometer. The performance of the time-of-flight mass spectrometer, i.e. the sensitivity of the spectrometer, the temporal resolution for fast concentration changes of the examined substances, and particularly the mass resolving power, relates critically to the transmission of the ions.
The invention consists of completely decelerating the ions by means of collisions with a damping gas in an RF ion guide system, guiding them to the end of the ion guide system by active forward thrust, extracting them by a drawing lens system, and forming an ion beam with a low phase space volume. In particular, the ion guide system can take the form of a pair of wires coiled in a double helix and be surrounded by an envelope which is filled with the damping gas.
Time-of-flight mass spectrometers with orthogonal injection of a primary ion beam have a so-called pulser at the beginning of the flight path, which accelerates a section of the primary ion beam, i.e. a thread-like ion package, at right angles to the previous direction of the beam. A band-shaped secondary ion beam is created in which light-weight ions fly fast and heavier ions fly more slowly, and the flight direction of which is between the previous direction of the primary ion beam and the perpendicular direction of acceleration. Such a time-of-flight mass spectrometer is preferably operated in conjunction with a velocity-focusing reflector which reflects the band-shaped secondary ion beam over its entire breadth and deflects it to an also extended detector
The mass resolution of such a time-of-flight mass spectrometer depends quite essentially on the spatial distribution and velocity distribution of the ions of the primary beam in the pulser.
If all the ions are flying exactly along an axis behind one another and if the ions do not have any velocity components at right angles to the primary ion beam, an infinitely high mass resolving power can, theoretically and very plausibly, be achieved because all the ions having the same mass are flying exactly in the same front and reach the detector at exactly the same time. If the primary ion beam has a finite cross section but none of the ions has a velocity component at right angles to beam direction, spatial focusing of the pulser can in turn theoretically bring about an infinitely high mass resolution (W. C Wiley and I. H. McLaren xe2x80x9cTime-of-Flight Mass Spectrometer with Improved Resolutionxe2x80x9d Rev. Scient. Instr. 26, 1150, 1955). The high mass resolution can even be achieved if there is a strict correlation between the ion location (measured from the beam axis of the primary beam in the direction of acceleration) and the perpendicular ion velocity in the primary beam in the direction of acceleration. If, however, there is no such correlation, i.e. if the ion locations and perpendicular ion velocities are statistically distributed without any correlation between the two distributions, high mass resolution can no longer be achieved.
The primary ion beam has therefore to be conditioned relative to spatial and velocity distribution in order to achieve a high mass resolution in the time-of-flight mass spectrometer.
In the simplest case such a conditioning can be achieved with two coaxial apertured diaphragms with very small holes, which only admit beam ions which are flying along very parallel axes and axes which are close to one another. In this case the conditioning takes place at the expense of ion transmission, and therefore at the expense of the sensitivity of such a mass spectrometer. Generally speaking, such a solution with low sensitivity is undesirable.
The six-dimensional space of spatial and pulse coordinates is called the xe2x80x9cphase spacexe2x80x9d. In an ion beam the spatial and pulse coordinates of all the ions fill out a certain part of the phase space and that part is called the xe2x80x9cphase space volumexe2x80x9d. Conditioning the primary beam therefore always means reducing phase space volume, at least in the coordinates at right angles to beam direction. A reduction in phase space volume cannot be achieved according to physical laws with ion-optical means but only by cooling the ion plasma of the ion beam, e.g. by cooling in a damping gas. Such cooling of the ions by a damping gas (at the expense of time) is known, for example, from high frequency quadrupole ion traps.
Time-of-flight mass spectrometers with orthogonal ion injection are preferably used for scanning high-resolution mass spectra with a fast spectrum sequence in order to be able to follow a separation of substances in fast methods of separation, capillary electrophoresis or microcolumn chromatography, for example, without any time smearing. Consequently, apart from high mass resolution, a high temporal resolution of subsequent substances is desirable. The cooling of the ions should therefore, if possible, take place by a continuous method which does not cause any mixing of earlier and later ions.
For time-of-flight mass spectrometers with preferably orthogonal injection an instrumental arrangement recently has became known from U.S. Pat. No. 6,011,259 (Whitehouse, Dresch and Andrien) in which multipole rod systems are used as ion guide systems (xe2x80x9cmultipole ion guidesxe2x80x9d), which guide ions from vacuum-external ion sources to the mass spectrometer and thus are also used for the selection of suitable parent ions and their fragmentation. The gas penetrating into the vacuum system together with the ions (usually nitrogen) is used as the collision gas for fragmentation, which also damps part of the motion of the ions but cannot be used systematically to reduce the phase space volume of the ions. Multipole rod systems used as ion guide systems do not have any active ion forward thrust; that is why in such systems the velocity must not be damped completely or else they can no longer pass through the ion guide system without mixing. On the other hand, they can be used as storage with requirement time-controlled outflow of the ions, but earlier and later ions mix and disturb the temporal resolution of fast chromatography and electrophoresis.
These multipole field ion guide systems consist of at least 2 pairs of straight pole rods which are evenly distributed over the surface of a cylinder and whose rods are alternately supplied with the two phases of an RF voltage. If there are two pairs of rods this is referred to as a quadrupole field, and if there are more than two pairs of rods they are referred to as hexapole, octopole, decapole, dodecapole fields etc. An ion-guiding dipole field with only one pair of rods cannot be generated. The fields are frequently termed 2-dimensional because in each cross section through the rod array the field distribution is the same. Consequently, field distribution only changes in two dimensions.
The RF multipole rod systems have become known as guide fields for ions between ion sources and ion consumers, particularly for feeding ions generated outside of the vacuum to RF or ICR ion traps inside vacuum systems.
The rod systems used for guiding ions are generally very slim in order to concentrate the ions in an area with a very small diameter. They can then advantageously be operated at low RF voltages and represent a good starting point for further ion-optical ion imaging. The clear cylindrical interior often only has a diameter of about 2 to 4 millimeters and the rods are less than 1 mm thick. The rods are usually fitted into grooves which are located inside of ceramic rings. The requirements for inside diameter uniformity, i.e. rod spacing, are relatively high. For this reason the system is not easy to make and it is also sensitive to vibrations and shock. The rod systems bend very easily and then they can no longer be adjusted.
On the other hand, U.S. Pat. No. 5,572,035 (Franzen) describes various ion guide systems which are completely different from the multipole rod systems described here. One of them consists of only 2 helically coiled conductors in the form of a double helix, which are operated by connecting up to the two phases of an RF voltage.
It is the aim of this invention to find methods and devices which condition the primary ion beam for time-of-flight mass spectrometers with orthogonal injection so that simultaneously a high sensitivity, high temporal resolution for changing ion compositions, and high mass resolution are achieved. For this the phase space volume in the primary ion beam must be reduced in particular.
The invention consists of using for the conditioning of the ions (a) an ion guide system of one of the known types, (b) completely damping the motion of the ions by filling gas so that they practically come to rest in the gas and gather along the axis of the ion guide system, (c) actively guiding the ions to the end of the ion guide system, (d) extracting them there through a drawing lens system, and (e) forming them into a conditioned beam of ions with a small phase space volume.
It is therefore particularly important to match the length of the ion guide system and the pressure of the damping gas to one another in such a way that the injected ionsxe2x80x94apart from thermal diffusion motionsxe2x80x94come to rest completely in the gas and collect along the axis of the ion guide system. Since the ions come to rest, it is necessary, by contrast with conventional use of such ion guide systems, to actively guide the ions to the end of the ion guide system.
The ion guide system can be a rod system supplied with RF voltages, whereby with four rods a quadrupole system can be built up, with six rods a hexapole system and with eight rods an octopole system. However, a simply constructed ion guide system in the form of a double helix, as described in U.S. Pat. No. 5,572,035 in detail, is particularly suitable for the present purpose.
Filling with gas can be achieved by operating the ion guide system in a vacuum chamber which is at a desired pressure of between 0.01 and 100 Pascal (preferably between 0.1 and 10 Pascal), or by at least partially enveloping the ion guide system so that only the envelope is filled with gas. The gas can then flow through the envelope and thus through the rod system or double helix.
The active forward thrust of the damped ions can take place in several ways: (1) the ions can most simply be driven by the introduced gas itself if the gas is fed in at the beginning of an envelope of the ion guide system and flows through the ion guide system to the end. (2) Due to a conical design of the ion guide system, a gentle forward thrust of the ions can be achieved. (3) The ion guide system can be provided with a weak axial DC field which guides the ions to the end of the ion guide system. For example, by supplying the pole rods or helical wires with a DC voltage, a voltage drop can be generated along the axis of the ion guide system. It is useful to make the pole rods or wires of the double helix from resistance wire. A very weak field of only approx. 0.01 to 1 volts per centimeter (preferably approx. 0.1 V/cm) is sufficient to provide the ions with forward thrust.
A drawing lens is an ion-optical lens which, at the same time as focusing (or defocusing), also imparts acceleration upon the ions. Both sides of the lens are therefore at different potentials. That is different from a so-called Einzel lens, which only has a focusing (or defocusing) effect but imparts no acceleration; the Einzel lens thus always has the same potential on both sides. Drawing lenses and Einzel lenses are generally made up of concentric apertured diaphragms at a fixed distance from one another. A drawing lens system is a system of ion-optical lenses in which at least one drawing lens is integrated; this means that a small-area location of origin of ions with uniform energy can be imaged at an even smaller-area image location (at the ion focus) with a narrow angle of focus or can also be transformed to a parallel beam with a narrow cross section.
A drawing lens can very efficiently withdraw the ions from the ion guide system if the potential of the second apertured diaphragm extends through the hole in the first apertured diaphragm into the ion guide system. The first apertured diaphragm is approximately at the axial potential of the ion guide. The hole in the second apertured diaphragm advantageously has a smaller diameter than that of the hole in the first apertured diaphragm. Also it is advantageous to design the three last diaphragms in the drawing lens system as an Einzel lens which handles the required focusing.
Since in the ion guide system a gas pressure prevails which is intentionally detrimental to ion motions but in a time-of-flight mass spectrometer a very good vacuum must prevail, these must be accommodated in separate vacuum chambers. Then it is advantageous to integrate the apertured diaphragm of the drawing lens system with the smallest hole into the wall between the vacuum chambers with a gastight seal. The diameter of the hole can be approx. 0.5 millimeters. To maintain a good pressure differential it is useful if the hole is made into a small duct. Two apertured diaphragms in the drawing lens system can also be used to generate a differential pump stage by pumping off between these two apertured diaphragms separately.
It is also helpful for maintaining a good pressure inside of the time-of-flight mass spectrometer if in the ion guide system the pressure of the damping gas decreases toward the end. This can be achieved if the gas is admitted at the beginning and if a pressure drop is created by openings in the envelope along the ion guide system.
The ion guide system can in particular also be used to fragment injected ions in order to scan their daughter ion spectra. The ions must then be injected with a kinetic energy which is sufficient for collisionally induced fragmentation. Here, for a good yield, but also for the downstream conditioning of the fragment ions, it is particularly important to decelerate the ions in the collision gas until they come to rest. The relatively slow guidance (in several milliseconds) of the ions, which are then practically at rest, toward the end of the ion guide system also helps to cool the daughter ions and cause short-living, highly excited daughter ions to decompose. As a result a daughter ion spectrum largely free of background noise is obtained in the time-of-flight spectrometer, which is not contaminated by scattered ions from ion decompositions during flight in the time-of-flight mass spectrometer.
To obtain clean daughter ion spectra without any extraneous companion ions it is useful to clean the wanted parent ions by removing all other companion ions. This is referred to as xe2x80x9cion selectionxe2x80x9d. This normally takes place using an upstream mass spectrometer. Here any continuous filtering mass spectrometers can be used, for example magnetic sector field mass spectrometers. However, linear mass spectrometers such as quadrupole filters or Wien filters are particularly suitable. A Wien filter is a superimposition of a magnetic field and an electric field in such a way that the selected ions fly straight ahead so their magnetic deflection is just compensated by the electric deflection.xe2x80x94Use of a first mass spectrometer for ion selection, a collision cell for fragmentation and a second mass spectrometer for analysis of the daughter or fragment ions is referred to as xe2x80x9ctandem mass spectrometryxe2x80x9d or xe2x80x9cMS/MSxe2x80x9d.
The parent ions can be selected in a variety of ways for generating daughter ions. All the isotope ions of a substance with the same charge can be selected, but also a single type of isotope (xe2x80x9cmonoisotopicxe2x80x9d ions).